Interferon has been shown to have a suppressive effect on several types of immune responses. We recently found that injection or induction of interferon in mice causes a marked inhibition of lymphocyte recirculation. Our major objectives are to define the mechanism of this interferon-mediated effect and determine its importance to the development of immune responses. Concerning the mechanism of inhibition, we have recent evidence that it does not interfere with the expression of sialic acid residues on the cell surface of the lymphocytes, nor does it involve the stimulation of corticosteroids. Concerning the localization of affected cells, we do not see any unusual accumulation of lymphocytes in any organ in mice treated systemically with PolyI:PolyC, which suggests that all cells are affected in situ. Recently, we have been able to obtain a localized lymphadenopathy by injection of PolyI:PolyC or interferon in the foot pad of a mouse. ln this way, trace studies have revealed a 2-\to 3-fold increase of labeled cells in the draining popliteal lymph node 22-48 hrs after injection. There is apparently no proliferation at this point because [unreadable]3[unreadable]H-Tdr uptake is normal. This would suggest that interferon does not affect actual entry of cells into the node but does block their capacity to exit along the efferent lymphatics. In addition, these studies suggest that both recombinant mouse gamma and purified beta interferons are capable of inducing the hypercellularity. With respect to immune responses, we have investigated the effect of Polyl:PolyC administration on the localized inflammatory response in the cerebral spinal fluid of mice injected intracerebrally with vaccinia virus. We have found that the response is significantly reduced, particularly in the participation of virus-specific cytotoxic T lymphocytes, whereas natural killer cell activity is enhanced. The inhibition is blocked with anti-interferon and is consistent with an effect on the ability of T cells to be recruited to the normally immune-privileged site. We will continue to examine these and related questions concerning the nature and effects of the interferon-mediated inhibition on recirculating lymphocytes. (HF)